Alternative splicing regulation by interaction of phosphatase PP2Cgamma with nucleic acid-binding protein YB-1

Allemand, E., Hastings, M. L., Murray, M. V., Myers, M. P., Krainer, A. R. (July 2007) Alternative splicing regulation by interaction of phosphatase PP2Cgamma with nucleic acid-binding protein YB-1. Nat Struct Mol Biol, 14 (7). pp. 630-638. ISSN 1545-9993 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/17572683
DOI: 10.1038/nsmb1257

Abstract

Kinases and phosphatases participate in precursor messenger RNA (pre-mRNA) splicing regulation, but their precise roles and the identities of their cofactors and substrates remain poorly understood. The human Ser/Thr phosphatase PP2Cgamma promotes spliceosome assembly. We show that PP2Cgamma's distinctive acidic domain is essential for its activity in splicing and interacts with YB-1, a spliceosome-associated factor. Moreover, PP2Cgamma is a phosphoprotein in vivo, and its acidic domain is phosphorylated under splicing conditions in vitro. PP2Cgamma phosphorylation enhances its interaction with YB-1 and is reversed by the phosphatase in cis. PP2Cgamma knockdown leaves constitutive splicing unaffected but inhibits cell proliferation and affects alternative splicing of CD44, a YB-1 target. This effect on splicing regulation is mediated by PP2Cgamma's acidic domain, which is essential to promote inclusion of CD44 exons v4 and v5 in vivo. We propose that PP2Cgamma modulates alternative splicing of specific pre-mRNAs coregulated by YB-1.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Alternative Splicing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > pre-mRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein phosphatase
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: CSHL Librarian
Date: July 2007
Date Deposited: 02 Dec 2011 15:28
Last Modified: 09 Apr 2014 14:16
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22957

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